We are studying the structure and function of malarial proteins inserted into and through the membrane of erythrocytes infected with mature asexual malaria parasites and molecules on the endothelial cells involved in cytoadherence. Five malarial proteins have been localized to the membrane of Plasmodium falciparum-infected erythrocytes at the mature trophozoite stage. The Mr approximately 300,000 cell surface protein associated with the property of cytoadherence to endothelial cells (denoted Pf EMP 1, P. falciparum erythrocyte membrane protein 1) has been shown to be antigenically distinct from another very large (Mr approximately 300,000) malarial protein located under the surface membrane in the electron-dense material at knobs (denoted Pf EMP 2). The histidine-rich protein (HRP) associated with knob expression (denoted PfHRP 1) was also shown to be localized under the membrane in the electron- dense material. Another HRP that is exported from infected cells into plasma (called Pf HRP 2) is also associated with the surface membrane, presumably en route for secretion since it is accessible to antibody at the cell surface and also attached to the cytoskeleton. We also showed that RESA, a protein inserted into the host membrane during merozoite invasion, remains in the membrane and is accessible to lactoperoxidase catalyzed radioiodination with trophozoite-infected cells.